Partitioning variance in cortical morphometry into genetic, environmental, and subject-specific components.

The relative contributions of genetic variation and experience in shaping the morphology of the adolescent brain are not fully understood. Using longitudinal data from 11,665 subjects in the ABCD Study, we fit vertex-wise variance components including family effects, genetic effects, and subject-level effects using a computationally efficient framework. Variance in cortical thickness and surface area is largely attributable to genetic influence, whereas sulcal depth is primarily explained by subject-level effects. Our results identify areas with heterogeneous distributions of heritability estimates that have not been seen in previous work using data from cortical regions. We discuss the biological importance of subject-specific variance and its implications for environmental influences on cortical development and maturation.

FEMA: Fast and efficient mixed-effects algorithm for large sample whole-brain imaging data.

The linear mixed-effects model (LME) is a versatile approach to account for dependence among observations. Many large-scale neuroimaging datasets with complex designs have increased the need for LME; however LME has seldom been used in whole-brain imaging analyses due to its heavy computational requirements. In this paper, we introduce a fast and efficient mixed-effects algorithm (FEMA) that makes whole-brain vertex-wise, voxel-wise, and connectome-wide LME analyses in large samples possible. We validate FEMA with extensive simulations, showing that the estimates of the fixed effects are equivalent to standard maximum likelihood estimates but obtained with orders of magnitude improvement in computational speed. We demonstrate the applicability of FEMA by studying the cross-sectional and longitudinal effects of age on region-of-interest level and vertex-wise cortical thickness, as well as connectome-wide functional connectivity values derived from resting state functional MRI, using longitudinal imaging data from the Adolescent Brain Cognitive DevelopmentSM Study release 4.0. Our analyses reveal distinct spatial patterns for the annualized changes in vertex-wise cortical thickness and connectome-wide connectivity values in early adolescence, highlighting a critical time of brain maturation. The simulations and application to real data show that FEMA enables advanced investigation of the relationships between large numbers of neuroimaging metrics and variables of interest while considering complex study designs, including repeated measures and family structures, in a fast and efficient manner. The source code for FEMA is available via: https://github.com/cmig-research-group/cmig_tools/.

Heritability Estimation of Cognitive Phenotypes in the ABCD Study® Using Mixed Models.

Twin and family studies have historically aimed to partition phenotypic variance into components corresponding to additive genetic effects (A), common environment (C), and unique environment (E). Here we present the ACE Model and several extensions in the Adolescent Brain Cognitive Development℠ Study (ABCD Study®), employed using the new Fast Efficient Mixed Effects Analysis (FEMA) package. In the twin sub-sample (n = 924; 462 twin pairs), heritability estimates were similar to those reported by prior studies for height (twin heritability = 0.86) and cognition (twin heritability between 0.00 and 0.61), respectively. Incorporating SNP-derived genetic relatedness and using the full ABCD Study® sample (n = 9,742) led to narrower confidence intervals for all parameter estimates. By leveraging the sparse clustering method used by FEMA to handle genetic relatedness only for participants within families, we were able to take advantage of the diverse distribution of genetic relatedness within the ABCD Study® sample.

Emotional changes following discrimination induction in gender- and sexuality-diverse adolescents.

Sexual and gender minority (SGM)-identifying adolescents are particularly vulnerable to negative psychological outcomes, including engagement in nonsuicidal self-injury (NSSI). However, little is known about why these relationships exist. We used experimental methods to test the psychological mediation framework in an online sample of 328 adolescents who reported female sex at birth and a range of sexual and gender identities. Participants reported on depressive symptoms, self-criticism (both self-report and implicit), NSSI, and discrimination. They also completed a discrimination-based mood induction to test emotional reactivity. At baseline, SGM participants reported higher levels of implicit and self-reported self-criticism, depressive symptoms, discrimination, and higher rates of NSSI compared with cisgender, heterosexual participants (ps < .03). Following the discrimination induction, SGM-identifying participants exhibited larger emotional reactivity compared with cisgender heterosexual participants, as measured by change in negative mood, F(1, 326) = 7.33, p = .01, ηp2 = .02, and state self-criticism, F(1, 326) = 4.67, p = .03, ηp2 = .014, but not implicit affect toward the self. This effect was associated with baseline depressive symptoms, self-criticism, NSSI history, and discrimination. Post hoc analyses revealed that participants who tended to reframe experiences of discrimination as opportunities for growth exhibited attenuated emotional reactivity to the induction; findings remained significant after adjusting for SGM status and event severity (ps < .001). Results indicate that adolescents identifying as SGM may experience elevated psychological distress compared with their cisgender heterosexual peers and that stigma-related stressors may increase emotion dysregulation and maladaptive cognitive styles, paralleling previously proposed psychological mediation models. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Online Methods in Adolescent Self-Injury Research: Challenges and Recommendations.

Online methods hold promise as effective research tools for adolescent psychopathology research. Such methods may be the most effective way to reach large, representative samples of adolescents and harder-to-reach populations. They also may increase adolescent disclosure of risky behaviors, reduce recruitment costs, and increase the cost and time efficiency of recruitment. Despite these advantages, researchers may be concerned about including measures assessing risky behaviors, like suicidal thoughts and behaviors and nonsuicidal self-injury, in online studies of youth. In addition, parental consent in online studies is impractical and difficult to obtain. Concerns also include potential iatrogenic effects, sample bias, and data quality issues. This review discusses the benefits and challenges for online adolescent self-injury research, proposes strategies to overcome barriers, and provides examples and recommendations for future research.

Pre-enlistment Anger Attacks and Postenlistment Mental Disorders and Suicidality Among US Army Soldiers.

Importance: Anger is linked to adverse outcomes in military populations; however, whether pre-enlistment anger attacks are associated with postenlistment mental disorders and suicidality is unknown. Objective: To explore the associations of pre-enlistment anger attacks with postenlistment mental health. Design, Setting, and Participants: In this observational cohort study, the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) New Soldier Study (NSS) surveyed soldiers entering basic training from April 2011 to November 2012, with a subsample recruited for wave 1 of the STARRS Longitudinal Study (STARRS-LS) (conducted September 2016 to April 2018). Participants were recruited from 3 US Army installations for the NSS survey. Those who were subsequently contacted for STARRS-LS completed the follow-up survey via web or telephone. Prospective analyses were based on a weighted NSS subsample included in wave 1 of STARRS-LS. Data were analyzed from May 22, 2020, to March 17, 2021. Exposures: History of anger attacks at baseline (NSS). Survey responses were used to classify new soldiers as having nonimpairing anger attacks (>2 attacks without interference in work or personal life), impairing anger attacks (>2 attacks with interference in work or personal life), or no significant history of anger attacks. Main Outcomes and Measures: Baseline analyses examined sociodemographic and clinical correlates of a history of anger attacks. Prospective logistic regression models estimated associations of baseline history of anger attacks with new onset and persistence of posttraumatic stress disorder, major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder, mania/hypomania, substance use disorder, suicidal ideation, and suicide attempt at wave 1 of STARRS-LS. Results: Of the 38 507 baseline participants (83.0% male and 17.0% female; mean [SD] age, 20.97 [3.57] years), 6216 were selected for and completed wave 1 of the STARRS-LS. Baseline prevalence (SE) of nonimpairing and impairing anger attacks was 8.83% (0.16%) and 5.75% (0.15%), respectively. Prospective models showed that impairing anger attacks were associated with new onset of MDD (adjusted odds ratio [AOR], 1.98; 95% CI, 1.31-2.99), GAD (AOR, 2.39; 95% CI, 1.66-3.45), panic disorder (AOR, 2.02; 95% CI, 1.34-3.05), and suicidal ideation (AOR, 2.11; 95% CI, 1.45-3.07). When baseline psychiatric comorbidity was controlled for, impairing attacks remained associated with onset of GAD (AOR, 1.75; 95% CI, 1.19-2.58) and suicidal ideation (AOR, 1.62; 95% CI, 1.09-2.42). Anger attacks were not significantly associated with persistence of pre-enlistment mental disorders. Conclusions and Relevance: The findings of this study suggest that a pre-enlistment history of impairing anger attacks may be associated with elevated risk of developing GAD, MDD, and suicidality after enlistment. Detection of impairing anger attacks could aid in assessing psychiatric risk in new soldiers.

Recurrent versus new-onset depressive symptoms: Relationships with biomarkers of cardiovascular health following acute coronary syndrome.

OBJECTIVE: New-onset depressive symptoms commonly arise among persons without a history of major depressive disorder (MDD) in the setting of acute medical illness. Although depressive symptoms in general are associated with alterations in prognostic biomarkers following acute coronary syndrome (ACS), the nature of specifically new-onset depressive symptoms is less well-characterized. It is unclear whether such symptoms neurobiologically resemble recurrent symptoms of MDD or instead represent a distinct condition. In this exploratory analysis, we aimed to examine the effects of prior MDD history on the relationships between post-ACS depressive symptoms and cardiovascular biomarkers. METHODS: One-hundred sixty-four participants attended study visits 2 weeks and 6 months after ACS to complete self-report measures and provide biomarker samples. MDD history was identified by a psychiatrist through systematic electronic medical record review. Generalized estimating equations were performed to examine the moderating effects of MDD history on concurrent relationships between depressive symptoms and several biomarkers (endothelin-1, soluble intercellular adhesion molecule-1, high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha). RESULTS: Twenty percent (n = 33) of participants had a history of MDD. Depressive symptoms were more strongly associated with levels of endothelin-1 in patients with prior MDD compared to those without (B = 0.024, 95% CI [0.005, 0.043], p = .012), adjusting for age, sex, medical factors, and anxiety. MDD history did not moderate relationships between depressive symptoms and other biomarkers. CONCLUSION: Recurrent post-ACS depressive symptoms are more strongly associated with elevated endothelin-1 levels than new-onset symptoms. Further work is needed to clarify the mechanism and clinical implications of this relationship.

Text Message Interventions for Physical Activity: A Systematic Review and Meta-Analysis.

CONTEXT: Despite clear health benefits, many individuals fail to achieve the recommended levels of physical activity. Text message interventions to promote physical activity hold promise owing to the ubiquity of cell phones and the low expense of text message delivery. EVIDENCE ACQUISITION: A systematic review and meta-analysis were performed to examine the impact of text message interventions on physical activity. Searches of PubMed, PsycINFO, Scopus, Cochrane, and ClinicalTrials.gov databases from inception to December 2017 were performed to identify studies investigating one-way text message interventionss to promote physical activity. A subset of RCTs, including an objective (accelerometer-based) physical activity outcome, were included in random-effects meta-analyses in 2018. EVIDENCE SYNTHESIS: The systematic search revealed 944 articles. Of these, 59 were included in the systematic review (12 1-arm trials and 47 controlled trials; n=8,742; mean age, 42.2 years; 56.2% female). In meta-analyses of 13 studies (n=1,346), text message interventionss led to significantly greater objectively measured postintervention steps/day (Cohen's d=0.38, 95% CI=0.19, 0.58, n=10 studies). Analysis of postintervention moderate-to-vigorous physical activity found a similar but not statistically significant effect (Cohen's d=0.31, 95% CI= -0.01, 0.63, n=5 studies). Interventions with more components, tailored content, and interventions in medical populations led to nonsignificantly larger effect sizes compared with text message interventions without these features. CONCLUSIONS: Text message interventions lead to higher objectively measured postintervention physical activity compared with control groups. More extensive, well-controlled studies are needed to examine this relationship further and identify characteristics of effective text message interventions.

Longitudinal predictors of self-injurious thoughts and behaviors in sexual and gender minority adolescents.

Sexual and gender minority (SGM) populations are at increased risk for several negative psychological outcomes, including self-injury. Although correlates of self-injurious thoughts and behaviors (SITBs) have been identified, it is unclear which factors are prospective predictors of SITB engagement in SGM youth. The current study investigated an online sample of 252 SGM adolescents over a 6-month period. Participants reported attitudes based on SGM identity, depression, self-criticism, body image, family support and family strain, friend NSSI engagement, and experiences of everyday discrimination. Lasso and elastic net regularized logistic regressions were used to examine which baseline variables were associated with SITB engagement at follow-up. Models resulted in excellent predictive accuracy of nonsuicidal self-injury and suicidal ideation (mean Area Under the Receiving Operating Characteristics Curve [AUC] of 0.90 and 0.91), good predictive accuracy for suicide plans (mean AUC = 0.85), and fair predictive accuracy for suicidal behaviors (mean AUC = 0.78). Several variables emerged as prospectively related to SITB risk, with varied associations across different SITBs. Results suggest that minority-specific factors may predict SITBs in SGM adolescents. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Does nonsuicidal self-injury prospectively predict change in depression and self-criticism?

Few studies have investigated nonsuicidal self-injury (NSSI) as a predictor of outcomes other than suicidal self-injury, severely limiting our understanding of this behavior's full range of consequences. Three independent studies were used to examine the prospective association between NSSI and two outcomes: depressive symptoms and self-criticism. Data were collected from samples of (1) adults with past-month NSSI, (2) adults with lifetime NSSI, and (3) adults with past-year NSSI. Studies included one-month and six-month follow-up periods. Results were tested in an internal meta-analysis. Results suggested that NSSI did not prospectively predict changes in self-criticism. No changes in depressive symptoms were seen over shorter follow-up periods; however, NSSI predicted increases in depressive symptoms at six-month follow-up in one sample. The internal meta-analysis indicated a null relationship between NSSI and prospective internalizing symptoms. Future research should replicate these findings and examine a broader range of outcomes of NSSI to better understand its complex relationship to psychopathology.

Self-Injurious Thoughts and Behaviors May Be More Common and Severe Among People Identifying as a Sexual Minority.

Research indicates that people who identify as a sexual minority are at higher risk of numerous negative outcomes, including self-injurious thoughts and behaviors (SITBs). The minority stress model proposes that people identifying as a sexual minority are at higher risk of these behaviors due to sexual orientation-specific stressors-however, it does not clarify whether SITBs will be more severe among these individuals. The present study tested whether SITBs are more common and more severe among people identifying as a sexual minority using several metrics, including frequency of SITB engagement, age of onset of SITB, desire to discontinue SITB engagement, and likelihood of future SITBs. Four independent research samples were used to test this model. Results were then combined and tested in an internal meta-analysis. Findings converge to indicate a longer and more severe course of SITB engagement among people identifying as a sexual minority. Future research is needed to replicate these findings and to advance the understanding of why this imbalance in risk and severity might exist, and how it can be prevented.

Surgical correction of a sacral meningomyelocele in a dog.

A 15 wk old male unilateral cryptorchid German shepherd dog weighing 18 kg was referred for a nonhealing cutaneous lesion dorsally at the level of the sacrum, urinary incontinence, and a deviated tail. MRI revealed spina bifida and meningomyelocele continuous with the skin surface. Surgical correction of the meningomyelocele involved closure of the open meningeal defect, transection of the abnormal spinal nerves to the skin surface, and closure of the skin defect with a good outcome. Histopathology confirmed a meningomyelocele. This case report describes the MRI findings, surgical procedure, and proposed pathogenesis of spina bifida and meningomyelocele in a dog.